Benzenamine, 4-(4-morpholinyl)- → 6-Methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide

HRID 2414533Notes

Reaction equation

HRID 2414533 reaction equation
C(OC1C=CC2SC([NH:12][C:13]([C:15]3[O:16][C:17]4[C:22]([C:23](=[O:25])[CH:24]=3)=[CH:21][CH:20]=[CH:19][C:18]=4[N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)=[O:14])=NC=2C=1)C.[O:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:46]=[CH:45][C:43](N)=[CH:42][CH:41]=2)[CH2:36][CH2:35]1.CN([C:50]([O:54]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH:69]1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[N:37]1([C:40]2[CH:46]=[CH:45][C:43]([NH:12][C:13]([C:15]3[O:16][C:17]4[C:22]([C:23](=[O:25])[CH:24]=3)=[CH:21][C:20]([O:54][CH3:50])=[CH:19][C:18]=4[N:26]3[CH2:31][CH2:69][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)=[O:14])=[CH:42][CH:41]=2)[CH2:38][CH2:39][O:34][CH2:35][CH2:36]1

Participants

6

Reactant 4

HCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 757711-HydroxybenzotriazoleHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 235333708-(4-Methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (5-ethoxy-benzothiazol-2-yl)-amide

Product 1

HCID 235333126-Methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amideYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 100 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer is added 327 mg (0.89 mmol, 1.0 equiv.) of 6-Methoxy-8-(4-methyl-[1,4]diazepan-1-yl)-4-oxo-4H-chromene-2-carboxylic acid hydrochloride salt (Reference Example 23). This material is dissolved in 20 mL of DMF and then 189 mg (1.06 mmol, 1.2 equiv.) of 4-morpholinoaniline is added. To the stirred solution is quickly added simultaneously added 568 mg (1.77 mmol, 2.0 equiv.) of TBTU and 239 mg (1.77 mmol, 2.0 equiv.) of HOBT. At this point 457 mg, 577 μL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes. The reaction is allowed to stir at room temperature for 18 hrs, then is concentrated on a rotary evaporator under high vacuum in order to remove the DMF. The residue is triturated with methanol and the crude solids are recovered by filtration. These residues are then purified by flash chromatography using a gradient of 5-10% methanol in methylene chloride as eluent. The eluted material, which is obtained from chromatography, is concentrated, dried under high vacuum, suspended in methylene chloride, dried over K2CO3, concentrated, then crystallized from methanol to give the free base of the pure product as 345 mg (79%) of a yellow solid. Mass Spec.: calc. for [C27H32FN4O5+H]+ Theor. m/z=393; Obs.=393.

Workup

  1. customInto a 100 mL round bottom flask equipped with a nitrogen inlet and magnetic stirrer
  2. additionAt this point 457 mg, 577 μL (25.2 mmol, 4.0 equiv.) is added via syringe over 5 minutes
  3. concentrationis concentrated on a rotary evaporator under high vacuum in order
  4. customto remove the DMF
  5. customThe residue is triturated with methanol
  6. filtrationthe crude solids are recovered by filtration
  7. customThese residues are then purified by flash chromatography
  8. customThe eluted material, which is obtained from chromatography
  9. concentrationis concentrated
  10. customdried under high vacuum
  11. dry with materialdried over K2CO3
  12. concentrationconcentrated
  13. customcrystallized from methanol

Sources & evidence

ORD record
ord-9cd62f72f5dd4c0e81ce7806a90f9efe
Source dataset
uspto-grants-2004_11
Patent number
US06812225B2

Reaction notes

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